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Ann Neurol. 2014 May;75(5):717-27. doi: 10.1002/ana.24162. Epub 2014 May 13.

Cortical interneuron loss and symptom heterogeneity in Huntington disease.

Author information

1
Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand; Centre for Brain Research, University of Auckland, Auckland, New Zealand.

Abstract

OBJECTIVE:

The cellular basis of variable symptoms in Huntington disease (HD) is unclear. One important possibility is that degeneration of the interneurons in the cerebral cortex, which play a critical role in modulating cortical output to the basal ganglia, might play a significant role in the development of variable symptomatology in HD. This study aimed to examine whether symptom variability in HD is specifically associated with variable degeneration of cortical interneurons.

METHODS:

We undertook a double-blind study using stereological cell counting methods to quantify the 3 major types of γ-aminobutyric acidergic interneurons (calbindin-D28k, calretinin, parvalbumin) in 13 HD cases of variable motor/mood symptomatology and 15 matched control cases in the primary motor and anterior cingulate cortices.

RESULTS:

In the primary motor cortex, there was a significant loss (57% reduction) of only calbindin interneurons (p=0.022) in HD cases dominated by motor symptoms, but no significant interneuron loss in cases with a dominant mood phenotype. In contrast, the anterior cingulate cortex showed a major significant loss in all 3 interneuron populations, with 71% loss of calbindin (p=0.001), 60% loss of calretinin (p=0.001), and 80% loss of parvalbumin interneurons (p=0.005) in HD cases with major mood disorder, and no interneuron loss was observed in cases with major motor dysfunction.

INTERPRETATION:

These findings suggest that region-specific degeneration of cortical interneurons is a key component in understanding the neural basis of symptom heterogeneity in HD.

PMID:
24771513
DOI:
10.1002/ana.24162
[Indexed for MEDLINE]

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